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Test Catalog

Test ID: HSMBS    
Hepatosplenomegaly Panel, Blood Spot

Useful For Suggests clinical disorders or settings where the test may be helpful

As a component of the initial evaluation of a patient presenting with hepatosplenomegaly

 

This test is not suitable for the identification of carriers.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Hepatosplenomegaly is a presenting or accompanying feature for many different inborn errors of metabolism. It typically is a consequence of chronic hepatic dysfunction or abnormal storage of lipids, sugars, or other improperly metabolized analytes due to a particular enzymatic deficiency. The diagnosis can occasionally be narrowed down by consideration of clinical symptoms; however, clinical diagnosis can be difficult due to similarity of clinical features across disorders, as well as phenotypic variability. Therefore, screening tests can play an important role in the workup of a patient with hepatosplenomegaly and a suspected lysosomal or lipid storage disorder.

 

The conditions detected in this assay are cerebrotendinous xanthomatosis, Gaucher disease, and Niemann-Pick disease types A, B, and C.

 

Conditions Identifiable By Method

Disorder

Onset

Analyte detected

Gene

Incidence

Cerebrotendinous Xanthomatosis (CTX)

 

 

 

Infancy-adulthood

7-alpha-hydroxy-4-cholesten-3-one (7a-C4)

7-alpha,12-alpha-dihydroxycholest-4-en-3-one (7a12aC4)

CYP27A1

1 in 50,000

As high as 1 in 400 in Druze population.

Phenotype: early onset diarrhea, cataracts, tendon/cerebral xanthomas, osteoporosis, neuropsychological manifestations, liver disease/hepatosplenomegaly.

Gaucher Disease

Type I: childhood/adult

Types II/III: neonatal-early childhood

glucopsychosine (GPSY)

GBA

Type I:

1 in 30,000 to 1 in 100,000

Types II/III:

1 in 100,000

Phenotype: all types exhibit hepatosplenomegaly and hematological abnormalities.

Type I: organomegaly, thrombocytopenia, and bone pain.  Absence of neurologic symptoms.

Types II/III: primary neurologic disease, developmental delay/regression, hepatosplenomegaly, lung disease. Patients with Type II typically die by age 2 to 4. Patients with Type 3 may have a less progressive phenotype and may survive into adulthood.

Niemann-Pick (NP) Type

A/B

NPA: neonatal

NPB: birth-adulthood

lyso-sphingomyelin (LSM)

lyso-sphingomyelin 509 (LSM 509)

SMPD1

Combined incidence

1 in 250,000

Phenotype:

NPA: feeding difficulties, jaundice, hepatosplenomegaly, neurologic deterioration, lung disease, hearing and vision impairment, cherry red macula, death usually by age 3.

NPB: mainly limited to visceral symptoms; hepatosplenomegaly, stable liver dysfunction, pulmonary compromise, osteopenia.

Niemann-Pick Type C

Variable

(perinatal-adulthood)

cholestane-3-beta, 5-alpha, 6-beta-triol (COT)

lyso-sphingomyelin 509 (LSM 509)

NPC1 or NPC2

1 in 120,000 to 1 in 150,000

Phenotype: Variable clinical presentation. Ataxia, vertical supranuclear gaze palsy, dystonia, progressive speech deterioration, seizures, +/- hepatosplenomegaly.

 

Patients with Fabry disease may also be identified by this assay. The glycosphingolipid, globotriaosylsphingosine (LGb3), may be elevated in symptomatic patients and supports a diagnosis of Fabry disease. Normal values of LGb3 do not rule-out Fabry disease. Patients with Fabry disease do not have hepatosplenomegaly as an accompanying feature.

 

Patients with testing indicative of 1 of the above disorders should have follow-up enzymatic or molecular testing for confirmation of diagnosis.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

CHOLESTANE-3-BETA, 5-ALPHA, 6-BETA-TRIOL

Cutoff: < or =0.800 nmol/mL

 

LYSO-SPHINGOMYELIN

Cutoff: < or =0.100 nmol/mL

 

GLUCOPSYCHOSINE

Cutoff: < or =0.040 nmol/mL

 

7-ALPHA-HYDROXY-4-CHOLESTEN-3-ONE (7a-C4)

Cutoff: < or =0.750 nmol/mL

 

7-ALPHA,12-ALPHA-DIHYDROXYCHOLEST-4-en-3-ONE (7a12aC4)

Cutoff: < or =0.250 nmol/mL

 

GLOBOTRIAOSYLSPHINGOSINE

Cutoff: < or =0.034 nmol/mL

Interpretation Provides information to assist in interpretation of the test results

An elevation of 7-alpha-hydroxy-4-cholesten-3-one (7a-C4) and 7-alpha,12-alpha-dihydroxycholest-4-en-3-one (7a12aC4) is strongly suggestive of cerebrotendinous xanthomatosis (CTX).

 

An elevation of lyso-sphingomyelin (LSM) and lyso-sphingomyelin 509 (LSM 509) is highly suggestive of Niemann-Pick type A or B (NPA or NPB) disease.

 

An elevation of cholestane-3-beta, 5-alpha, 6-beta-triol (COT) lyso-sphingomyelin 509 (LSM 509) is highly suggestive of Niemann-Pick disease type C (NPC).

 

An elevation of glucopsychosine is indicative of Gaucher disease.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Patients with Wolman disease or cholestatic biliary atresia may have a profile similar to Niemann-Pick disease type C (NPC).

 

Patients with bile acid malabsorption or ileal resection may have elevations of 7-alpha-hydroxy-4-cholesten-3-one (7a-C4).

 

This test does not identify all causes of hepatosplenomegaly.

 

A positive test result is strongly suggestive of a diagnosis but needs follow-up by stand-alone biochemical or molecular assay.

 

This test should not be used as a monitoring tool for patients with confirmed diagnoses.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. DeBarber AE, Luo J, Star-Weinstock M, et al: A blood test for cerebrotendinous xanthomatosis with potential for disease detection in newborns. J. Lipid Res 2014;55:146-154

2. Federico A, Dotti MT, Gallus GN: Cerebrotendinous Xanthomatosis. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al. Updated 2016 Apr14. University of Washington, Seattle. 1993-2019. Available at www.ncbi.nlm.nih.gov/books/NBK1409/

3. Grabowski GA, Petsko GA, Kolodny EH, et al:. et al: Gaucher disease. In The Online Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein, et al. New York, McGraw-Hill, 2014. Accessed August 11, 2017. Available at http://ommbid.mhmedical.com/content.aspx?bookid=971&sectionid=62643884

4. Murugeasan V, Chuan WL, Liu J, et al: Glucosylsphingosine is a key biomarker of Gaucher disease. Am J Hematol 2016; 91(11)1082-1089

5. Patterson M: Niemann-Pick disease type C. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al. Retrieved April 7, 2017. Available at www.ncbi.nlm.nih.gov/books/NBK1296/

Special Instructions Library of PDFs including pertinent information and forms related to the test